In the classical adenoma-carcinoma sequence of colorectal carcinogenesis, what is the correct order of genetic events?
- A KRAS mutation, then APC loss, then p53 loss
- B p53 loss, then APC loss, then KRAS mutation
- C APC loss, then KRAS mutation, then p53 loss ✓
- D APC loss, then p53 loss, then KRAS mutation
Correct answer: C. APC loss, then KRAS mutation, then p53 loss
Explanation
APC loss initiates the pathway by disabling the Wnt signalling brake, producing an early adenoma. KRAS activation follows and drives growth into a larger adenoma, while loss of p53 accompanies the transition from late adenoma to carcinoma. KRAS mutation cannot initiate the sequence because its downstream effect requires prior APC loss, which eliminates the most tempting distractor ordering.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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